1. Field of the Invention
This invention relates to deoxy, amino derivatives of idose and glucose which exhibit immunomodulatory, anti-inflammatory, and anti-proliferative activity. Compounds of the invention are useful for treating mammals with inflammatory and/or autoimmune disorders. This invention also relates to pharmaceutical compositions containing the disclosed compounds and to methods of a treating inflammatory and/or autoimmune disorders employing the disclosed compounds.
2. Description of the Related Art
Derivatives of certain monosaccharides are known to have therapeutic value in the treatment of inflammatory and autoimmune disorders. Preparation of derivatives of these sugars can generally be accomplished by synthetic techniques which are known in the art.
To prepare derivatives of the monosaccharides, it is common to block or protect one or more of the hydroxyl groups with acetal blocking groups such as isopropylidene or cyclohexylidene groups and leave only one or two hydroxyl groups free to undergo further reaction. Various blocking groups and methods are described in U.S. Pat. Nos. 2,715,121 and 4,056,322 and the disclosures of these patents are incorporated herein by reference. For example, to prepare a derivative of .alpha.,D-glucose which is blocked in its furanose ring structure, the 1,2- and 5,6-hydroxyl groups can be blocked using an isopropylidene blocking group and the 3-position left open to undergo further reaction. After the reaction to derivatize the 3-position is complete, the blocking groups may be selectively removed to allow for further derivatization at other positions if desired.
Various derivatives of monosaccharides, as well as synthetic methods for their preparation, are described in U.S. Pat. Nos. Re. 30,354, Re. 30,379, Re. 32,268, 4,056,322, 4,735,934, 4,738,953, 4,996,195, 5,010,058, and 5,298,494. The therapeutic activity of various monosaccharides and their derivatives is also disclosed in these documents. The disclosures of these documents are incorporated herein by reference.
Two well known derivatives of .alpha.,D-glucose having beneficial therapeutic properties are amiprilose, which is 1,2-O-Isopropylidene-3-O-3'-(N,N'-dimethylamino-n-propyl)-.alpha., D-glucofuranose, and its hydrochloric acid salt, amiprilose HCl (THERAFECTIN.RTM.). These compounds are known to have anti-inflammatory activity and demonstrate utility in managing the signs and symptoms of rheumatoid arthritis. More generally, these compounds have activity as immunomodulators, and therefore have a therapeutic effect on autoimmune disorders such as, for example, rheumatoid arthritis and psoriasis.
Deoxy derivatives of 1,2-O-Isopropylidene-.alpha.,D-glucofuranose are described in U.S. Pat. No. 5,010,058, the disclosure of which is incorporated herein by reference. That patent describes methods of preparing deoxy derivatives of 1,2-0-Isopro-pylidene-.alpha., D-glucofuranose, and the use of such compounds in treating mammals with inflammatory and/or autoimmune disorders.
While some prior art monosaccharide derivatives have shown beneficial therapeutic activity, high doses of such compounds may often be needed to be effective and produce the desired results. Because therapy for inflammatory and autoimmune disorders is often chronic, there is a continuing need to develop potent, nontoxic compounds which can be orally administered to promote ease of treatment and patient compliance.
The present invention, therefore, is directed to new compounds and pharmaceutical compositions that exhibit greater potency than available compounds and compositions.
The present invention is also directed to a method of treating an animal or human suffering from an inflammatory and/or autoimmune disorder.
Other advantages of the invention are set forth in the description which follows, will be apparent from the description, or may be learned by practice of the invention.